Phase 3 Study to Evaluate the Acid-Inhibitory Effect of Multiple Oral Doses of Vonoprazan (TAK-438)

NCT02037477 | Completed Phase 3 Results

• 5 other identifiers: TAK-438/CPH-010U1111-1152-3926NCT02037477JapicCTI-142411JapicCTI-R150821
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to investigate the acid-inhibitory effect of multiple oral doses of Vonoprazan (TAK-438) and the relative effect of vonoprazan versus two controls (esomeprazole and rabeprazole sodium) in healthy Japanese adult male participants with the CYP2C19 extensive metabolizer (EM) genotype.

Conditions

Healthy Volunteers

Outcome Measures

Primary Outcomes (1)

• Intragastric pH Time Course Over 24 Hours

  Intragastric pH was measured continuously for 24 hours (hr) by pH monitor. pH holding time ratio (HTR) is the percentage of time a pH is maintained at a particular level. For example, pH 4 HTR is the percentage of time the pH = 4.

  At baseline (Day -2 to Day -1), administration period (Days 1 to Day 2 and Days 7 to Day 8)

Secondary Outcomes (4)

• Frequency of Adverse Events

  31 days

• Number of Participants With Abnormal Changes From Baseline in Vital Signs

  At screening, baseline (Day -3, Day -2, Day -1), administration period (Days 1, Day 2, Day 7, Day 8), and post-test (Day 28)

• Number of Participants With Abnormal 12-lead Electrocardiogram (at Rest) Findings

  At Screening, baseline (Day -3), administration period (Day 8), and post-test (Day 28)

• Number of Participants With Markedly Abnormal Laboratory Values

  At Screening, baseline (Day -3), administration period (Day 1, Day 8), and post-test (Day 28)

Study Arms (4)

Sequence A (Cohort 1): Vonoprazan + Esomeprazole

EXPERIMENTAL

Vonoprazan (TAK-438) 20 mg, orally, once daily for 7 days, followed by a washout period of at least 7 days; then esomeprazole 20 mg, orally, once daily for 7 days.

Drug: Vonoprazan; Drug: Esomeprazole

Sequence B (Cohort 1): Esomeprazole + Vonoprazan

EXPERIMENTAL

Esomeprazole 20 mg, orally, once daily for 7 days, followed by a washout period of at least 7 days; then vonoprazan 20 mg, orally, once daily for 7 days.

Drug: Vonoprazan; Drug: Esomeprazole

Sequence C (Cohort 2): Vonoprazan + Rabeprazole Sodium

EXPERIMENTAL

Vonoprazan 20 mg, orally, once daily for 7 days, followed by a washout period of at least 7 days; then Rabeprazole sodium 10 mg, orally, once daily for 7 days.

Drug: Vonoprazan; Drug: Rabeprazole sodium

Sequence D (Cohort 2): Rabeprazole Sodium + Vonoprazan

EXPERIMENTAL

Rabeprazole sodium 10 mg, orally, once daily for 7 days, followed by a washout period of at least 7 days; then vonoprazan 20 mg, orally, once daily for 7 days.

Drug: Vonoprazan; Drug: Rabeprazole sodium

Interventions

Vonoprazan DRUG

Vonoprazan tablets

Also known as: TAK-438, Takecab®

Sequence A (Cohort 1): Vonoprazan + Esomeprazole; Sequence B (Cohort 1): Esomeprazole + Vonoprazan; Sequence C (Cohort 2): Vonoprazan + Rabeprazole Sodium; Sequence D (Cohort 2): Rabeprazole Sodium + Vonoprazan

Esomeprazole DRUG

Esomeprazole capsules

Also known as: Nexium (esomeprazole)

Sequence A (Cohort 1): Vonoprazan + Esomeprazole; Sequence B (Cohort 1): Esomeprazole + Vonoprazan

Rabeprazole sodium DRUG

Rabeprazole sodium tablets

Also known as: Pariet (rabeprazole)

Sequence C (Cohort 2): Vonoprazan + Rabeprazole Sodium; Sequence D (Cohort 2): Rabeprazole Sodium + Vonoprazan

Eligibility Criteria

• Age: 20 Years - 45 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Is a healthy Japanese adult male volunteer.
• Is aged 20 to 45 years, inclusive, at the time of informed consent.
• Has been confirmed at CYP2C19 genotyping as an Extensive Metabolizer \[EM (\*1/\*1,\*1/\*2,\*1/\*3)\].
• Capable of understanding and complying with the protocol requirements.
• The participant signs and dates a written informed consent form prior to the initiation of any study procedures.
• Weighs 50 kg or more and has body mass index (BMI) of 18.5 or more and less than 25.0 kg/m\^2 at Screening or admission (Day -3).
• H. pylori-negative at Screening.

You may not qualify if:

• Has undergone resection of the upper gastrointestinal tract or vagotomy.
• Was determined to have hypoacidity or anacidity.
• Has a present or past history of acid-related disease (reflux esophagitis, gastric ulcer, duodenal ulcer, non-erosive gastroesophageal reflux, Barrett's esophagus, Zollinger-Ellison syndrome, etc.).
• Has undergone eradication of H. pylori within 6 months prior to the start of the study drug administration.
• Has uncontrolled, clinically significant neurologic, cardiovascular, pulmonary, hepatic, renal, metabolic, gastrointestinal, or endocrine disease or other abnormalities which may impact the ability of the subject to participate or potentially confound the study results.
• Has a known hypersensitivities or allergies to drugs or food.
• Has a history of drug abuse (defined as any illicit drug use) or a history of alcohol abuse within 5 years prior to the start of the study drug administration.
• Has poor peripheral venous access.
• Had 200 mL or more of whole blood drawn within 4 weeks (28 days) prior to the start of the study drug administration or 400 mL or more of whole blood drawn within 12 weeks (84 days) prior to the start of the study drug administration.
• Had a total volume of 800 mL or more of whole blood drawn within 52 weeks (364 days) prior to the start of the study drug administration.
• Has undergone blood component draw within 2 weeks (14 days) prior to the start of the study drug administration.
• Requires treatment with any of the excluded medications specified in the study or requires nutrition with any vitamin supplements or foods prohibited in the study.
• Has received study medication within 16 weeks (112 days) prior to the start of the study drug administration.
• Has received vonoprazan (TAK-438) in the past.
• Has a history of cancer.

Sponsors & Collaborators

• Takeda: lead

Study Sites (1)

Unknown Facility

Fukuoka, Fukuoka, Japan

Location

MeSH Terms

Interventions

1-(5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl)-N-methylmethanamine; Esomeprazole; Rabeprazole

Intervention Hierarchy (Ancestors)

Omeprazole; 2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Medical Director, Clinical Science
• Organization: Takeda

trialdisclosures@takeda.com

+1-877-825-3327

Study Officials

• General Manager

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 14, 2014
• First Posted: January 16, 2014
• Study Start: January 1, 2014
• Primary Completion: March 1, 2014
• Study Completion: March 1, 2014
• Last Updated: October 17, 2016
• Results First Posted: October 17, 2016

Record last verified: 2016-08

Locations

JP (1)